title: Dramatically stabilizing multiprotein complex structure in the absence of bulk water using tuned Hofmeister salts.
abstract: The role that water plays in the salt-based stabilization of proteins is central to our understanding of protein biophysics. Ion hydration and the ability of ions to alter water surface tension are typically invoked, along with direct ion-protein binding, to describe Hofmeister stabilization phenomena observed for proteins experimentally, but the relative influence of these forces has been extraordinarily difficult to measure directly. Recently, we have used gas-phase measurements of proteins and large multiprotein complexes, using a combination of innovative ion mobility (IM) and mass spectrometry (MS) techniques, to assess the ability of bound cations and anions to stabilize protein ions in the absence of the solvation forces described above. Our previous work has studied a broad set of 12 anions bound to a range of proteins and protein complexes, and while primarily motivated by the analytical challenges surrounding the gas-phase measurement of solution-phase relevant protein structures, our work has also lead to a detailed physical mechanism of anion-protein complex stabilization in the absence of bulk solvent. Our more-recent work has screened a similarly-broad set of cations for their ability to stabilize gas-phase protein structure, and we have discovered surprising differences between the operative mechanisms for cations and anions in gas-phase protein stabilization. In both cases, cations and anions affect protein stabilization in the absence of solvent in a manner that is generally reversed relative to their ability to stabilize the same proteins in solution. In addition, our evidence suggests that the relative solution-phase binding affinity of the anions and cations studied here is preserved in our gas-phase measurements, allowing us to study the influence of such interactions in detail. In this report, we collect and summarize such gas-phase measurements to distill a generalized picture of salt-based protein stabilization in the absence of bulk water. Further, we communicate our most recent efforts to study the combined effects of stabilizing cations and anions on gas-phase proteins, and identify those salts that bear anion/cation pairs having the strongest stabilizing influence on protein structures
authors.affiliation: Department of Chemistry, University of Michigan, 930 N. University Ave., Ann Arbor, MI 48109, USA.
authors.forename: Linjie
authors.initials: L
authors.lastname: Han
authors.forename: Suk-Joon
authors.initials: SJ
authors.lastname: Hyung
authors.forename: Brandon T
authors.initials: BT
authors.lastname: Ruotolo
mesh_terms: D013058:Mass Spectrometry; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D012492:Salts / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D011506:Proteins; D012492:Salts; D014867:Water